The Role of MRI Lesions in Identifying Secondary Progressive Multiple Sclerosis: A Comprehensive Review

Abstract

Secondary Progressive Multiple Sclerosis (SPMS) represents a challenging phase of multiple sclerosis, marked by gradual neurological decline and reduced inflammatory activity. In recent years, magnetic resonance imaging (MRI) has become essential for characterizing the neurodegenerative changes underlying SPMS, including white and gray matter damage, brain atrophy, slowly expanding lesions, and iron rim lesions. This narrative review aims to synthesize the current knowledge on established and emerging MRI biomarkers relevant to SPMS, with a particular focus on their diagnostic, prognostic, and therapeutic implications. This review discusses key themes, such as the shift from inflammatory to neurodegenerative mechanisms, the role of advanced imaging techniques, and the limitations of conventional MRI in detecting smoldering disease. In doing so, it identifies current gaps in evidence, including the need for standardized imaging protocols and large-scale longitudinal studies. A clearer understanding and application of MRI biomarkers may facilitate earlier diagnosis, more tailored treatment strategies, and improved outcomes in patients with SPMS.

Keywords: MRI lesions; gray matter atrophy; iron rim lesions; secondary progressive multiple sclerosis; slowly expanding lesions; spinal cord lesions.

Figure 1

Axonal loss due to demyelination. Over time, this leads to brain atrophy and irreversible neurological deficits.

Figure 2

White matter lesions. The grey area represents the brain tissue, and the bright white areas represent the white matter lesions. These lesions are typically hyperintense (brighter) on T2-weighted MRI scans and represent areas of damage to the myelin sheath, which insulates nerve fibers in white matter. The red arrow indicates one of these distinct bright white lesions. In SPMS, these lesions indicate demyelination, axonal loss, and gliosis.

Figure 3

Chronic active lesions. The background grey represents the brain tissue. The areas highlighted with a color gradient (from blue to red) represent chronic active lesions, also known as “smoldering lesions.” These lesions are characterized by persistent, low-level inflammation. Although they may not appear as intensely bright as typical acute white matter lesions, these areas indicate ongoing damage. In more advanced MRI techniques (not directly shown in this illustrative style), these lesions often show a dark rim, indicative of chronic inflammation.